We have been developing tools and applications for structure-based drug design. On the development side, we've designed the de novo drug design program BUILDER. BUILDER is an interactive model building program run from within MIDAS. Its purpose is to design novel lead drug compounds, given the 3-D structure of the target receptor. Its approach to drug design is to first analyze the receptor for "hot spots" or areas of good potential drug interaction, such as hydrophobic pockets or possible H-bonding sites. Then BUILDER selects appropriate small molecules or fragments to be placed at each of these "hot spots" to maximize drug-receptor binding. Finally, the small molecules or fragments are linked together in a chemically sensible way to form a whole molecule. All steps in this process are displayed on MIDAS, so they can be interactively directed and controlled by the user. The program uses the new delegate feature of MIDAS to allow interactive use. It has been tested and found to be capable of rebuilding methotrexate from the 4dfr receptor. The CGL facility is vital to this project, since the program needs to be run interactively on the MIDAS graphics program. In applications, the program BUILDER has used to help design a combinatorial library for cathepsin D. This results have been synthesized and are currently being tested. Also, the program DOCK has been applied to DNA, to examine 1) if it can correctly predict binding of known DNA binding compounds 2) if it can discriminate molecules that will preferentially bind to one form (A,B,Z) of DNA. Again, CGL is necessary in applications as all results need to be examined and evaluated using computer graphics.